title: KRAS and MAPK1 gene amplification in type II ovarian carcinomas.
abstract: In this study, we examined the clinical significance of KRAS and MAPK1 amplification and assessed whether these amplified genes were potential therapeutic targets in type II ovarian carcinoma. Using fluorescence in situ hybridization, immunohistochemistry, and retrospectively collected clinical data, KRAS and MAPK1 amplifications were identified in 9 (13.2%) and 5 (7.4%) of 68 type II ovarian carcinoma tissue samples, respectively. Interestingly, co-amplification of KRAS and MAPK1 seemed to be absent in the type II ovarian carcinomas tested, except one case. Active phospho-ERK1/2 was identified in 26 (38.2%) out of 68 type II ovarian carcinomas and did not correlate with KRAS or MAPK1 amplification. There was no significant relationship between KRAS amplification and overall or progression-free survival in patients with type II ovarian carcinoma. However, patients with MAPK1 amplification had significantly poorer progression-free survival than patients without MAPK1 amplification. Moreover, type II ovarian carcinoma cells with concomitant KRAS amplification and mutation exhibited dramatic growth reduction following treatment with the MEK inhibitor PD0325901. These findings indicate that KRAS/MAPK1 amplification is critical for the growth of a subset of type II ovarian carcinomas. Additionally, RAS/RAF/MEK/ERK pathway-targeted therapy may benefit selected patients with type II ovarian carcinoma harboring KRAS/MAPK1 amplifications.
authors.affiliation: Departments of Obstetrics and Gynecology, Shimane University School of Medicine, Enyacho 89-1, Izumo, Shimane 6938501, Japan. kn88@med.shimane-u.ac.jp.
authors.forename: Mohammed Tanjimur
authors.initials: MT
authors.lastname: Rahman
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Munmun
authors.initials: M
authors.lastname: Rahman
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katagiri
authors.forename: Atsuko
authors.initials: A
authors.lastname: Katagiri
authors.forename: Tomoka
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Masako
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Emi
authors.initials: E
authors.lastname: Sato
authors.forename: Kouji
authors.initials: K
authors.lastname: Iida
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakayama
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins